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Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

Primary Purpose

B Cell Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Waldenstrom Macroglobulinemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AVL-292
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B Cell Non-Hodgkin's Lymphoma focused on measuring non-hodgkin's lymphoma, lymphoma, leukemia, chronic lymphocytic leukemia, b-cell malignancies, Btk inhibitor, Phase 1b, Avila Therapeutics, Waldenstrom Macroglobulinemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Women and men ≥18 years of age
  • Body weight ≥50 kg.
  • Confirmed diagnosis of B cellNon-Hodgkin Lymphoma(according to World Health Organization [WHO] classification)including Chronic Lymphocytic Leukemia/Small cell Lymphocytic Leukemia (International Workshop),or Waldenstrom's Macroglobulinemia(Second International Workshop)
  • Have failed ≥1 previous treatment for B-NHL/CLL/WM, and have relapsed or refractory disease following last prior treatment.
  • Eastern Cooperative Oncology Group performance status of ≤ 2 and a life expectancy of at least 3 months.
  • Ability to swallow oral capsules without difficulty
  • Has recovered from adverse toxic effects of prior therapies

  • Meet the following clinical laboratory requirements:

    • Creatinine ≤ 1.5 × upper limit of normal (ULN)
    • Total bilirubin ≤ 1.5 x ULN
    • AST and ALT ≤ 3 × ULN
    • Platelet count ≥ 50,000/µL (non-hodgkin & Waldenstrom's)
    • Platelet count ≥ 30,000/µL (chronic lymphocytic leukemia)
    • Absolute Neutrophil count ≥ 1000/µL

Exclusion Criteria:

  • Prior allogeneic bone marrow transplant
  • Autologous stem cell transplant within 3 months of screening
  • Active central nervous system involvement
  • Subjects with autoimmune hemolytic anemia or immune thrombocytopenia
  • Prior treatment with a Btk inhibitor
  • Active uncontrolled infection
  • History of malabsorption
  • Uncontrolled illness, i.e cardiac, endocrine, respiratory, etc.
  • History of myocardial infarction, acute coronary syndromes, coronary angioplasty and/or stenting with in the previous 6 months
  • History of another currently active cancer
  • History of major surgery within 4 weeks or minor surgery within 1 week
  • Other medical or psychiatric illness or organ dysfunction
  • HIV positive
  • Positive for Hepatitis B surface antigen or Hepatitis C-virus

Sites / Locations

  • Clearview Cancer Institute Oncology Specialties, P.C
  • University of Arizona SPORE
  • University of California San Diego
  • Mayo Clinic Jacksonville
  • Northwestern University
  • Horizon Oncology Center
  • Dana Farber Cancer Institute
  • Mount Sinai School of Medicine and Mount Sinai Graduate School of Biological Sciences
  • University of Rochester Medical Center
  • Cleveland Clinic
  • The University of Texas MD Anderson Cancer Center
  • University of Texas Health Sciences Center
  • US Oncology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AVL-292

Arm Description

Outcomes

Primary Outcome Measures

Safety, tolerability,and dose limiting toxicities will be determined using AEs,PE,ophthalmologic examinations,clinical laboratory tests,vital signs, ECGs and echocardiograms/MUGA scans.

Secondary Outcome Measures

Establish recommended Phase 2 dose, after completing dose escalation in Part 1 and evaluating accumulated safety,PK,and PD data from the dose escalation phase (Part1)
After completion of observation for dose limiting toxicities in Part 1 of the study, the accumulated safety, PK, and PD data from Part 1 will be evaluated by the investigators and Sponsor to select a preliminary RP2D for administration to additional subjects to be enrolled into 1 of 3 independent and non-randomized diagnosis-specific expansion cohorts in Part 2 of the study
Evaluate the Pharmacokinetic parameters of AVL-292
Serial blood sampling to enable PK characterization of AVL-292 will be performed for the Cycle1 Day 1 (C1D1) and Cycle 1Day 15 dose administrations. Additional samples will be obtained on C1D8 and C1D22.A non-compartmental model will be evaluated for all subjects.
Evaluate the Pharmacodynamics of AVL-292 by measurement of free Btk
The PD activity of AVL-292 will be studied with a quantitative assay using a covalent probe to directly assess free Btk in PBMC lysates.
Characterize preliminary anti-tumor efficacy of AVL-292 in relapsed and/or refractory B-NHL, CLL and WM
Efficacy response assessments will be formally assessed within 7 days preceding C2D1, C3D1, C5D1, C7D1, and EOT

Full Information

First Posted
May 10, 2011
Last Updated
November 6, 2019
Sponsor
Celgene
Collaborators
The Leukemia and Lymphoma Society
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1. Study Identification

Unique Protocol Identification Number
NCT01351935
Brief Title
Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia
Official Title
Phase 1b, Escalating Dose Study of AVL-292, a Bruton's Tyrosine Kinase (Btk) Inhibitor, as Monotherapy in Subjects With Relapsed and/or Refractory B Cell Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
July 18, 2011 (Actual)
Primary Completion Date
June 26, 2015 (Actual)
Study Completion Date
June 26, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
Collaborators
The Leukemia and Lymphoma Society

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety and tolerability of AVL-292 as monotherapy in subjects with relapsed or refractory B cell non-Hodgkin lymphoma (B-NHL), chronic lymphocytic leukemia (CLL) or Waldenstrom's macroglobulinemia (WM).
Detailed Description
Bruton's tyrosine kinase (Btk) is non-receptor tyrosine kinase with restricted cellular expression largely limited to B-lymphocytes, monocytes, and mast cells or basophils. Btk is a critical component of the B cell receptor (BCR) signaling network and is crucial for B cell development. Investigation has revealed that some B cell lymphomas and CLL depend on BCR signaling, suggesting that interruption of such signaling could be a promising therapeutic opportunity in B-NHL, CLL and WM.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B Cell Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, Waldenstrom Macroglobulinemia
Keywords
non-hodgkin's lymphoma, lymphoma, leukemia, chronic lymphocytic leukemia, b-cell malignancies, Btk inhibitor, Phase 1b, Avila Therapeutics, Waldenstrom Macroglobulinemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
113 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AVL-292
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
AVL-292
Other Intervention Name(s)
Btk inhibitor
Intervention Description
125 mg to 625 mg orally, once a day, for 28 days (28 days equals 1 cycle). Number of cycles: until progression or unacceptable toxicity develops
Primary Outcome Measure Information:
Title
Safety, tolerability,and dose limiting toxicities will be determined using AEs,PE,ophthalmologic examinations,clinical laboratory tests,vital signs, ECGs and echocardiograms/MUGA scans.
Time Frame
with in the first 28 days after initiation of once daily oral dosing
Secondary Outcome Measure Information:
Title
Establish recommended Phase 2 dose, after completing dose escalation in Part 1 and evaluating accumulated safety,PK,and PD data from the dose escalation phase (Part1)
Description
After completion of observation for dose limiting toxicities in Part 1 of the study, the accumulated safety, PK, and PD data from Part 1 will be evaluated by the investigators and Sponsor to select a preliminary RP2D for administration to additional subjects to be enrolled into 1 of 3 independent and non-randomized diagnosis-specific expansion cohorts in Part 2 of the study
Time Frame
Completion of Part 1 dose escalation phase of study
Title
Evaluate the Pharmacokinetic parameters of AVL-292
Description
Serial blood sampling to enable PK characterization of AVL-292 will be performed for the Cycle1 Day 1 (C1D1) and Cycle 1Day 15 dose administrations. Additional samples will be obtained on C1D8 and C1D22.A non-compartmental model will be evaluated for all subjects.
Time Frame
First 28 days of dosing
Title
Evaluate the Pharmacodynamics of AVL-292 by measurement of free Btk
Description
The PD activity of AVL-292 will be studied with a quantitative assay using a covalent probe to directly assess free Btk in PBMC lysates.
Time Frame
First 28 days of dosing
Title
Characterize preliminary anti-tumor efficacy of AVL-292 in relapsed and/or refractory B-NHL, CLL and WM
Description
Efficacy response assessments will be formally assessed within 7 days preceding C2D1, C3D1, C5D1, C7D1, and EOT
Time Frame
After completion of 28 day cycle of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Women and men ≥18 years of age Body weight ≥50 kg. Confirmed diagnosis of B cellNon-Hodgkin Lymphoma(according to World Health Organization [WHO] classification)including Chronic Lymphocytic Leukemia/Small cell Lymphocytic Leukemia (International Workshop),or Waldenstrom's Macroglobulinemia(Second International Workshop) Have failed ≥1 previous treatment for B-NHL/CLL/WM, and have relapsed or refractory disease following last prior treatment. Eastern Cooperative Oncology Group performance status of ≤ 2 and a life expectancy of at least 3 months. Ability to swallow oral capsules without difficulty Has recovered from adverse toxic effects of prior therapies Meet the following clinical laboratory requirements: Creatinine ≤ 1.5 × upper limit of normal (ULN) Total bilirubin ≤ 1.5 x ULN AST and ALT ≤ 3 × ULN Platelet count ≥ 50,000/µL (non-hodgkin & Waldenstrom's) Platelet count ≥ 30,000/µL (chronic lymphocytic leukemia) Absolute Neutrophil count ≥ 1000/µL Exclusion Criteria: Prior allogeneic bone marrow transplant Autologous stem cell transplant within 3 months of screening Active central nervous system involvement Subjects with autoimmune hemolytic anemia or immune thrombocytopenia Prior treatment with a Btk inhibitor Active uncontrolled infection History of malabsorption Uncontrolled illness, i.e cardiac, endocrine, respiratory, etc. History of myocardial infarction, acute coronary syndromes, coronary angioplasty and/or stenting with in the previous 6 months History of another currently active cancer History of major surgery within 4 weeks or minor surgery within 1 week Other medical or psychiatric illness or organ dysfunction HIV positive Positive for Hepatitis B surface antigen or Hepatitis C-virus
Facility Information:
Facility Name
Clearview Cancer Institute Oncology Specialties, P.C
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35805
Country
United States
Facility Name
University of Arizona SPORE
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
University of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0960
Country
United States
Facility Name
Mayo Clinic Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Horizon Oncology Center
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Mount Sinai School of Medicine and Mount Sinai Graduate School of Biological Sciences
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Texas Health Sciences Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
US Oncology
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77380
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27471698
Citation
Arnason JE, Brown JR. B cell receptor pathway in chronic lymphocytic leukemia: specific role of CC-292. Immunotargets Ther. 2014 Jan 24;3:29-38. doi: 10.2147/ITT.S37419. eCollection 2014.
Results Reference
background
Links:
URL
http://www.lls.org/
Description
Leukemia & Lymphoma Society

Learn more about this trial

Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia

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